Neuronal loss in man, whether by disease, aging, or accident is permanent. Central Nervous System (CNS) neurons, when damaged, have a very limited regenerative ability. However, recent studies from our laboratory and from others, have demonstrated that transplanted neurons can reinnervate injured areas of the brain under some conditions. We have developed a model system for analyzing the functional development of grafted CNS neurons which involves transplanting vasopressin neurons from the hypothalamic neurosecretory system of normal donors into Brattleboro rats, that congenitally lack vasopressin-producing neurons. Amelioration of the symptoms of diabetes insipidus in the host is then evaluated as a correlate of the function of the transplant. We intend to continue testing this model system to define the important variables involved in the functional development of transplanted hypothalamic neurons. The experiments detailed in the present proposal are designed to (i) determine the optimal procedures for transplantation in order to assure transplant function; (ii) examine the ability of grafted vasopressin neurons to respond to normal physiological and pharmacological stimuli and (iii) utilize state-of-the-art electronic cell sorting procedures to obtain enriched populations of vasopressin neuron for transplantation. The goal of the latter experiment is to develop the ability to transpolant relatively pure populations of vasopressing neurons rather than the mixed populations of glia and neurons found in the anterior hypothalamus. The techniques necessary to accomplish these goals (e.g.) microsurgery, neural grafting, cell separation and culture, neuropeptide immunocytochemistry, vasopressing radioimmunoassay) are in use in our laboratories.